Written by Peter Liu
Spoon Feed
Prasugrel is making a comeback as a P2Y12 inhibitor that is likely superior to ticagrelor in modern acute coronary syndrome (ACS) care.
Prasugrel vs ticagrelor – reproducible benefit is king
P2Y12 platelet inhibition is a cornerstone of modern ACS care, reducing cardiovascular thrombotic events (recurrent MI, in-stent thrombosis, stroke, and mortality) at the cost of increased bleeding risk. Clopidogrel, ticagrelor, and prasugrel are the most commonly used options in the U.S.. Recent prescribing been influenced by the PLATO trial, which showed that ACS patients undergoing percutaneous coronary intervention (PCI) had decreased thrombotic events with ticagrelor compared to clopidogrel, without a significant increase in bleeding outcomes. Compared to the results of TRITON-TIMI 38, which showed that prasugrel had a similar antithrombotic benefit to clopidogrel but with increased bleeding events, ticagrelor seemed to be superior. However, evidence is mounting that prasugrel may be superior to ticagrelor. This is based primarily on three developments regarding this issue:
- There is concern for misreporting of PLATO data, which favored the pharmaceutical sponsors of the trial.
- The key findings in PLATO have not been reproducible, despite multiple similar trials.
- In a head-to-head comparing ticagrelor to prasugrel in a high quality RCT, ISAR-REACT5 showed that prasugrel had better ACS outcomes without increased bleeding in patients, with most undergoing PCI.
The featured study today was a propensity-matched cohort analysis comparing prasugrel to ticagrelor in patients with ACS and found the composite outcome of all-cause mortality, MI, or stroke favored prasugrel: 9.2% (ticagrelor) vs. 7.5% (prasugrel), HR 1.24 (95%CI 1.12-1.37). It’s an observational study, but because results were similar to ISAR-REACT5, it provides strong support for prasugrel over ticagrelor as the P2Y12 inhibitor of choice, particularly in STEMI patients undergoing PCI. We’ll see if future studies corroborate these findings.
How does this change my practice?
While my own hospitalist practice will likely remain unchanged, I anticipate more patients with ACS will be treated with prasugrel in the future. This study helps explain why.
Source
Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care. JAMA Netw Open. 2024 Dec 2;7(12):e2448389. doi: 10.1001/jamanetworkopen.2024.48389. PMID: 39621344
